IGF-I inhibits apoptosis through the activation of the phosphatidylinositol 3-kinase/Akt pathway in pituitary cells

Fernández, Miriam; Sánchez‐Franco, Franco; Palacios, Nuria; Sánchez, Israel M.; Fernández, Cecilia A.; Cacicedo, Lucinda

doi:10.1677/jme.0.0330155

Cited by 47 publications

(32 citation statements)

References 37 publications

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“…It has been well recognized that IGF-1 inhibits serum deprivation-induced apoptosis in many cell types including IVD cells [6,[35][36][37][38][39][40][41], probably through the phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways [35,36,[38][39][40][41]. In addition, there is evidence showing that IGF-1 can also inhibit IL-1b-induced apoptosis in some cell types, such as growth plate chondrocytes from metatarsal bones [42] and pancreatic beta cells [43,44], probably by preventing the Fas-mediated component.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1β enhances the effect of serum deprivation on rat annular cell apoptosis

Zhao

et al. 2007

Apoptosis

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Excessive apoptosis of disc cells is believed to play an important role in intervertebral disc (IVD) degeneration. It has been shown that interleukin-1beta (IL-1beta) is involved in the failure of disc matrix by suppressing the synthesis of matrix components and stimulating the expression of matrix metalloproteinases. However, whether IL-1beta induces disc cell apoptosis is still unclear. The objective of this study was to investigate the effect of IL-1beta on the apoptosis of rat annular cells cultured with or without serum supplement. First-passage rat annular cells were cultured with 0% or 10% fetal bovine serum (FBS) supplement and stimulated with 0, 10, 20 or 50 ng/ml IL-1beta for 12, 24 or 48 h. Apoptotic incidences were quantified by flow cytometry, morphologic changes in apoptotic cells were visualized by Hoechst 33258 staining and phase-contrast microscopy, and caspase-3 activity was also determined. When rat annular cells were cultured with 10% FBS supplement, no significant changes in apoptotic incidences, apoptotic morphology and caspase-3 activity were observed even when cells were stimulated with 50 ng/ml IL-1beta for 48 h. In contrast, serum deprivation for 24 h led to an increase in apoptotic incidences, the number of apoptotic nuclei and caspase-3 activity, and IL-1beta significantly increased the effects of serum deprivation in a dose-dependent manner. Our results indicate that IL-1beta alone is not a sufficient stimulus to induce disc cell apoptosis and that in order to suppress disc cell apoptosis, improving the nutrient supply to the disc may be more effective than antagonizing the adverse effects of IL-1beta.

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Section: Discussionmentioning

confidence: 99%

Interleukin-1β enhances the effect of serum deprivation on rat annular cell apoptosis

Zhao

et al. 2007

Apoptosis

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“…In addition, high glucose-induced apoptosis could be prevented by insulin-like growth factor-I (IGF-I), which caused phosphorylation of Bad at Ser 112 in a process carried out by IGF-I-stimulated ERK [42]. This is interesting because the majority of data to date suggest that the antiapoptotic effect of IGF-I is mediated predominantly by PI-3-kinase/Akt and is independent of MEK/ERK [43,44]. In practice, it is likely that one or both of these mechanisms is activated by IGF-I depending on cell type and duration of exposure to high glucose concentrations.…”

Section: Mitochondria-dependent and -Independent Mechanismsmentioning

confidence: 99%

Mechanisms of high glucose-induced apoptosis and its relationship to diabetic complications

Allen

Yaqoob

Harwood

2005

The Journal of Nutritional Biochemistry

215

156

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“…Insulin-like growth factor (IGF)-I modulates pituitary cell turnover and function (Oomizu et al 1998, Fernandez et al 2004 and acts through the Akt and MAPK signalling pathways. As circulating IGF-I levels are reduced in diabetes (Olchovsky et al 1991, Busiguina et al 1996 and decreased IGF-I signalling has been implicated in increased apoptosis in various tissues in response to diabetes (Russell et al 1999, Gerhardinger et al 2001, it is conceivable that it plays an important role in the modification of cell turnover in the pituitary of diabetic rats.…”

Section: Introductionmentioning

confidence: 99%

Cell-specific expression of X-linked inhibitor of apoptosis in the anterior pituitary of streptozotocin-induced diabetic rats

Arroba

Frago

Argente

et al. 2007

Journal of Endocrinology

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Cell death is increased in the anterior pituitary of poorly controlled diabetic rats, but anti-apoptotic mechanisms are also activated. We hypothesized that specific cell types are selectively protected against diabetes-induced cell death. To determine when anti-apoptotic mechanisms are activated, streptozotocin-induced diabetic rats were killed after 1, 4, 6 and 8 weeks of evolution. Anterior pituitaries were processed for western blot analysis to determine changes in the intrinsic cell death pathway and upstream kinases involved in cell protection mechanisms. An increase in cell death was detected by ELISA at 4 weeks of diabetes. TUNEL labelling demonstrated that this corresponded to death of primarily lactotrophs, a few somatotrophs, and no thyrotrophs, corticotrophs or gonadotrophs. Levels of phosphorylated (p) Akt were increased at 1 week of diabetes, while pERK1/2 levels increased at 4 weeks and pJNK at 6 weeks. Activation of caspase 3 decreased and anti-apoptotic members of the Bcl-2 protein family increased as early as 1 week after diabetes onset. These changes were coincident with increased IGF-I receptor levels. Levels of X-linked inhibitor of apoptosis protein (XIAP) increased significantly after 6 weeks of diabetes, as did activation of nuclear factor (NF)kB. Double immunohistochemistry indicated that XIAP was expressed in less than 1% of lactotrophs and gonadotrophs, approximately 50% of somatotrophs and more than 90% of corticotrophs and thyrotrophs. These results suggest that some cell survival mechanisms are rapidly activated in the anterior pituitary, even before increased cell death can be detected, while others are more delayed. Furthermore, both pituitary cell death and expression of protective mechanisms such as XIAP are celltype specific.

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IGF-I inhibits apoptosis through the activation of the phosphatidylinositol 3-kinase/Akt pathway in pituitary cells

Cited by 47 publications

References 37 publications

Interleukin-1β enhances the effect of serum deprivation on rat annular cell apoptosis

Interleukin-1β enhances the effect of serum deprivation on rat annular cell apoptosis

Mechanisms of high glucose-induced apoptosis and its relationship to diabetic complications

Cell-specific expression of X-linked inhibitor of apoptosis in the anterior pituitary of streptozotocin-induced diabetic rats

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